DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application filed 09/08/2023 is a National Stage entry of PCT/US2022/019992, with an International Filing Date of 03/11/2022. The claims are therefore examined as filed on 03/11/2022, the effective filing date. In future actions, the effective filing date of one or more claims may change, due to amendments to the claims, or further review of the priority application(s).
Claim Status
Claims 1-6, 10, 15, 25, 32-34, 37-42, and 45-46 are pending.
Claims 10, 25, 33, 39, and 46 are objected to.
Claims 7-9, 11-14, 16-24, 25, 31, 35-36, 43-44, and 47-151 are cancelled.
Claims 1-6, 10, 15, 25, 32-34, 37-42, and 45-46 are examined.
Claims 1-6, 10, 15, 25, 32-34, 37-42, and 45-46 are rejected.
Information Disclosure Statement
The Information Disclosure Statements are in compliance with the provisions of 37 CFR 1.97. Accordingly, all references have been considered.
Drawings
The drawings are objected to because many of the figures contain burry and/or illegible text. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because it contains embedded hyperlinks and/or other forms of browser-executable code (see page 71). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claims 10, 25, 33, 39, and 46 are objected to because of the following informalities:
Claim 10 should read “wherein obtaining a TCRβ gene sequence comprises sequencing TCRβ genes [[is]]in a blood sample from a subject.
Claim 25 part a) should read “classifying T cell receptor β (TCRβ) genes of the donor and TCRP genes of the recipient as productive TCRβ genes or repaired TCRβ genes…”
Claim 25 part c) should also read “quantifying the fraction of TCRβ genes from the donor that are compatible with the recipient…”
Claim 33 should read “quantifying a number of repaired TCRβ genes from the donor…”
Claim 39 part a) should read “classifying T cell receptor β (TCRβ) genes of a hematopoietic cell donor and TCRP genes of a hematopoietic cell recipient as productive TCRβ genes or repaired TCRβ genes…”
Claim 46 should read “The method of claim 45, wherein the first three amino acids and the last three amino acids of the CDR3 sequences from the TCRB gene sequence are removed.”
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 15, 25, 32-34, 37-42 and 45-46 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 15 is unclear as it recites the limitation "the method of claim 1, wherein the subject is human". There is insufficient antecedent basis for this limitation in the claim, as claim 1 makes no mention of a subject. Therefore this claim is indefinite due to lack of clarity.
Claims 25 and 39 are also unclear because they are multiple dependent claims containing the step of “classifying T cell receptor β (TCRβ) genes…using the method of any one of claims 4-15…”. The dependency is unclear as claims 7-9 and 11-14 are cancelled. Therefore these claims are also indefinite due to lack of clarity.
Dependent claims 32-34, 37-38, 40-42 and 45-46 are also unclear as they do not resolve the issues above, and are also therefore indefinite due to lack of clarity.
Claim 37 is also unclear with respect to the phrase “the method of claim 25, wherein the TCRβ gene sequence comprises a CDR3 sequence of the TCRβ gene.” Claim 25 refers to multiple TCRβ genes, so it is unclear if the sequence in claim 37 refers to just one of the genes of claim 25, or to each gene classified in claim 25. Claim 38 is similarly unclear as it refers to “the TCRB gene sequence” of claim 37.
Claim 45 is also unclear with respect to the phrase “the method of claim 39, wherein the TCRβ gene sequence comprises a CDR3 sequence of the TCRβ gene.” Claim 39 refers to multiple TCRβ genes, so it is unclear if this refers to one of the genes of claim 39, or to each gene classified in claim 39. Claim 46 is similarly unclear as it refers to “the TCRB gene sequence” of claim 45.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-6, 10, 15, 25, 32-34, 37-42, and 45-46 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea of mental processes and mathematical concepts, without significantly more.
The MPEP at MPEP 2106 sets forth steps for identifying eligible subject matter:
(1) Are the claims directed to a process, machine, manufacture or composition of matter?
(2A)(1) Do the claims recite a judicially recognized exception, i.e. a law of nature, a natural phenomenon, or an abstract idea?
(2A)(2) Do the claims recite additional elements that integrate the judicial exception into a practical application?
(2B) If the claims recite a judicial exception and do not integrate the judicial exception, do the claims recite additional elements that provide an inventive concept and amount to significantly more than the judicial exception?
With regard to step (1) (Are the claims directed to a process, machine, manufacture or composition of matter?): Yes. The claims are directed to one of the statutory classes. Claims 1-6, 10, 15, 25, 32-34, 37-42, and 45-46 are directed to processes (methods).
With regard to step (2A)(1) (Do the claims recite a judicially recognized exception?): Yes. The claims recite the abstract ideas of processing data using mental steps and mathematical concepts. Claims that recite nothing more than abstract ideas, natural phenomena, or laws of nature are not eligible for patent protection (see MPEP 2106.04).
Abstract ideas include mathematical concepts, (mathematical formulas or equations, mathematical relationships and mathematical calculations), certain methods of organizing human activity, and mental processes (including procedures for collecting, observing, evaluating, and organizing information (See MPEP 2106.04(a)(2)). In particular, these abstract ideas include but are not limited to:
Translating one of multiple gene segments or somatic alterations from a gene sequence into an amino acid sequence (mental process; the human mind is capable of translating a segment of a gene sequence into an amino acid sequence, as it is known which codons translate into which amino acids; claims 1, 25, 39)
Identifying an immune receptor chain gene encoding an amino acid sequence capable of antigen recognition as a productive immune receptor chain gene, and identifying an immune receptor chain gene without an amino acid sequence capable of antigen recognition as a non-productive immune receptor chain gene (mental process; the human mind is capable of identifying a sequence based on whether or not it encodes a sequence with certain properties; claims 1, 25, 39)
Repairing the amino acid sequence of an immune receptor chain gene identified as non- productive to generate a repaired immune receptor chain gene capable of antigen recognition (mental process; the human mind is capable of changing a sequence to generate a difference sequence, where the sequences result in different structures/properties when translated; the specification indicates that this is done using an algorithm and not by physical gene editing; claims 1, 25, 39)
Classifying the immune receptor chain gene as a productive immune receptor chain gene or as a repaired immune receptor chain gene (mental process; the human mind is capable of classifying data based on its properties; claims 1, 25, 39)
Comparing a number of productive and repaired TCRβ genes in the recipient to a number of productive TCRβ genes in the doner (mental process; the human mind is capable of making a comparison/comparing genes; claim 25)
Quantifying the fraction of TCRβ from the donor that are compatible with the recipient, where the quantifying comprises calculation a post selection fraction score (mental process/mathematical concept; the human mind is capable of quantifying data/a sequence based on compatibility, and calculating a score is a mathematical process; claims 25, 33-34)
Comparing a number of repaired TCRβ genes in both a hematopoietic stem cell donor and a hematopoietic stem cell recipient (mental process; the human mind is capable of making a comparison/comparing genes; claim 39)
Quantifying a number of repaired TCRβ genes in the hematopoietic stem cell donor that are not found in the hematopoietic stem cell recipient, wherein quantifying comprises calculating a fNOVEL score (mental process/mathematical concept; the human mind is capable of quantifying data/a sequence based on whether the sequence is found is a patient, and calculating a score is a mathematical process; claims 39, 42)
Dependent claims 2-6, 15, 32, 37-38, and 40-41 further limit the abstract ideas recited in the independent claims, and do not change their characterization as abstract ideas.
Therefore, the claims recite elements that constitute one or more judicial exceptions.
With regard to step (2A)(2) (Do the claims recite additional elements that integrate the judicial exception into a practical application?): No. Claim 1 and its dependents recite the additional element of obtaining an immune receptor chain gene sequence comprising multiple gene segments and somatic alterations. Claim 10 further recites that this obtaining comprises sequencing TCRβ genes in a blood sample from a subject.
While the claims recite the additional element of obtaining data, such steps that only amount to necessary data gathering , without any technical details of how the data is obtained that integrate the judicial exception, are insignificant extrasolution activities that do not add a meaningful limitation to the claims (see MPEP 2106.05(g)). As a result, the judicial exception is not integrated into a practical application. Because the claims do not recite any additional elements that integrate the judicial exception into a practical application, the claims as a whole are directed to an abstract idea.
With regard to step (2B) (Do the claims recite additional elements that provide an inventive concept and amount to significantly more than the judicial exception?): No.
The claims recite an abstract idea with an additional element; however, this additional element is a non-particular instruction to apply the abstract idea by linking it to a field of use or extrasolution activity (see MPEP 2106.05(f-h)). Such non-particular instructions to gather data for analysis do not provide an inventive concept. Non-particular instructions to gather data by sequencing are also considered well-understood, routine and conventional activities (see MPEP 2106.05(d), which indicates that limitations such as “Analyzing DNA to provide sequence information or detect allelic variants”, from Genetic Techs. Ltd., 818 F.3d at 1377; 118 USPQ2d at 1546, and “Amplifying and sequencing nucleic acid sequences”, from University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014) are recognized as conventional activities). The claims therefore do not include additional elements that are sufficient to amount to significantly more than the judicial exception. As a result, the claims as a whole do not provide an inventive concept.
Claims Without an Art Rejection
No art rejection is applied to claims 1-6, 10, 15, 25, 32-34, 37-42, and 45-46. Close art includes ZHANG 2018 (US 20180201991 A1, as cited on the IDS filed 12/14/2023), which teaches obtaining a T cell receptor by sequencing and translating the sequencing read to identify CDR3 candidates, YIU (as cited on the IDS filed 12/14/2023) which teaches sequencing TCR sequences and classifying them as productive or non-productive groups due to frame shift or early stop codons, and HOU (as cited on the IDS filed 12/14/2023) which similarly teaches sequencing of TCR-b repertoires and classifying TCR-B chains as productive or non-productive. However, these do not teach the instant combination of repairing the amino acid sequence of an immune receptor chain gene identified as non- productive to generate a repaired immune receptor chain gene capable of antigen recognition, and classifying the immune receptor chain gene as a productive immune receptor chain gene or as a repaired immune receptor chain gene, and no combinable art before the effective filing date could be found to render the claims as obvious.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
MURUGAN 2012 “Statistical inference of the generation probability of T-cell receptors from sequence repertoires” teaches the use of statistical inference methods predicts the generation probability of any specific CDR3 sequence by the primitive recombination process
KRANGEL 2009 “Mechanics of T cell receptor gene rearrangement” teaches mechanisms influencing activation and inactivation of T cell receptor locus recombination events
DEAN 2015 “Annotation of pseudogenic gene segments by massively parallel sequencing of rearranged lymphocyte receptor loci” teaches determining the presence and the proportion of productive rearrangements for TCRβ V gene segments in individual and using this to annotate the functional status of TCRβ V gene segments
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARY C LEVERETT whose telephone number is (571)272-5494. The examiner can normally be reached 8:00am - 5:00pm M-Th.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Karlheinz R. Skowronek can be reached at (571) 272-9047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARY C LEVERETT/Examiner, Art Unit 1687
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